Research progress on substitution of in vivo method(s) by in vitro method(s) for human vaccine potency assays

ABSTRACT

Introduction

Potency is a critical quality attribute for controlling quality consistency and relevant biological properties of vaccines. Owing to the high demand for animals, lengthy operations and high variability of in vivo methods, in vitro alternatives for human vaccine potency assays are extensively developed.

Areas covered

Herein, in vivo and in vitro methods for potency assays of previously licensed human vaccines were sorted, followed by a brief description of the background for substituting in vivo methods with in vitro alternatives. Based on the analysis of current research on the substitution of vaccine potency assays, barriers and suggestions for substituting were proposed.

Expert opinion

Owing to the variability of in vivo methods, the correlation between in vivo and in vitro methods may be low. One or more in vitro method(s) that determine the vaccine antigen content and functions, should be established. Since the substitution involves with the change of critical quality attributes and specifications, the specifications of in vitro methods should be appropriately set to maintain the efficacy of vaccines. For novel vaccines in research and development, in vitro methods for monitoring the consistency and relevant biological properties, should be established based on reflecting the immunogenicity of vaccines.

KEYWORDS:

• Human vaccines
• potency
• in vivo potency
• in vitro potency
• method substitution
• 3Rs

Article highlights

• During the process of vaccine batch release, potency is a critical quality attribute (CQA) to control quality consistency and relevant biological properties. Potency assays of vaccines may be conveniently divided into in vivo methods (animal-based) and in vitro methods (non-animal-based).

• Owing to the characteristics and tradition of vaccines, in vivo methods which have high variability are widely adopted for vaccine potency assays.

• With the implementation of GMP and 3Rs principles, in vivo methods with inherent variability, may be considered inferior to monitoring the consistency of production. Therefore, it is imperative to substitute the in vivo methods.

• A single in vitro method based on neutralizing antibodies or multiple in vitro methods can improve the sensitivity and reduce the time required.

• The substitution of in vivo methods with in vitro methods accompanies with the change of CQAs and specifications. The specifications of in vitro methods should be appropriately set to maintain the efficacy of vaccines.

• For novel vaccines in research and development (R&D), in vitro methods for monitoring the consistency and relevant biological properties should be established based on reflecting the immunogenicity of vaccines.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

X Zhang and X Wu conceived and drafted the manuscript; Q He and J Wang provided valuable discussion; M Xu, Z Liang and Q Mao revised the manuscript. All authors have read and approved the article.

Additional information

Funding

This manuscript was funded by the CAMS Innovation Fund for Medical Sciences (2021-I2M-5–005).